The main objectives of this project are to determine whether DES is metabolized to biologically and hormonally active metabolites; to test the hypothesis that certain chemicals are "transplacental toxicants" due to their relative binding to plasma/receptor proteins particularly alpha-fetoprotein; to investigate some of the biochemical mechanisms which contribute to effects of prenatal exposure of mice to hormonally active environmental chemicals, to investigate the mechanism of uterine hormonal responsiveness and to determine the molecular locus of transplacental toxicity using structure-function relationships of different environmental chemicals; and to determine biochemical markers for transplacental toxicity. These objectives are approached using refined biochemical techniques of hormone receptors and hormone action. The basic physiological effects on hormone synthesis and hormone levels will be studied using chemical extraction techniques and radioimmunoassays. The carcinogenic nature of hormonally active environmental chemicals will be studied in vivo.